Synopsis
Select evidence-based non-hormonal treatment for vasomotor, sleep and mood symptoms when HRT is unsuitable or not preferred, including the March 2026 NICE fezolinetant pathway and safe medicine monitoring.
- Offer menopause-specific CBT for vasomotor symptoms, either alongside HRT or when HRT is contraindicated or declined.
- NICE TA1143 recommends fezolinetant for moderate to severe menopausal vasomotor symptoms when HRT is unsuitable.
- Fezolinetant is 45 mg once daily; liver tests and CYP1A2 interactions are central to safe prescribing.
- Do not routinely offer an SSRI, SNRI or clonidine as first-line treatment for vasomotor symptoms alone.
- An antidepressant may still be appropriate for a diagnosed depressive or anxiety disorder, selected under the relevant guideline.
- Gabapentin can reduce flushes but sedation, falls, renal dose adjustment, dependence and withdrawal limit its use.
- Clonidine has modest benefit and can cause dry mouth, constipation, sedation, hypotension and bradycardia; taper rather than stop abruptly.
- As of 31 August 2026, elinzanetant is UK-licensed but its two NICE appraisals remain awaiting development; check commissioning and the current SmPC rather than treating licensing as a national recommendation.
Key red flags
Jaundice, dark urine, pale stools, right-upper-quadrant pain or unexplained marked fatigue while taking fezolinetant
ALT or AST above five times the upper limit of normal, or at least three times the limit with bilirubin above twice the limit or liver symptoms
Suicidal thoughts, severe depression, mania, psychosis or inability to maintain personal safety
Fever, agitation, clonus and autonomic instability after a serotonergic medicine change
Syncope, severe postural hypotension, new bradycardia or conduction symptoms during clonidine
A new seizure, collapse or altered consciousness while taking elinzanetant requires urgent neurological and medicine assessment
New focal neurological deficit, chest pain, breathlessness, pelvic mass symptoms or unexplained weight loss that should not be labelled as menopause
Investigation priorities
Establish a baseline frequency and functional burden and identify triggers or previous responses.
Management branches
Vasomotor symptoms are troublesome and HRT is contraindicated, unsuitable or declined.
- Confirm a menopausal pattern, identify alternative diagnoses and agree whether flush frequency, sleep or distress is the primary outcome.
- Offer menopause-specific CBT and practical symptom strategies, addressing access, language, disability and digital-exclusion needs.
- Review after an agreed course using baseline symptom and function measures; add or switch treatment if benefit is insufficient.
CBT and the preferred licensed pathway do not meet need or another condition creates a therapeutic reason for a different medicine.
- Treat diagnosed depression or anxiety under its own guideline; consider tamoxifen, blood pressure, renal function, falls, dependence and withdrawal risks.
- Agree that any off-label vasomotor trial has one target, a cautious titration and a defined review date rather than stacking several sedating medicines.
- Continue only if benefit is meaningful; taper venlafaxine, gabapentin or clonidine